Improved Survival With Higher Tumor-Infiltrating Lymphocyte Values in Advanced HER2-Positive Breast Cancer
In a retrospective analysis of the phase III CLEOPATRA trial reported in The Lancet Oncology, Luen et al found that higher baseline tumor-infiltrating lymphocyte levels were associated with improved overall survival among patients with advanced HER2-positive breast cancer receiving trastuzumab (Herceptin)/docetaxel plus pertuzumab (Perjeta) or placebo. As a result, the investigators suggest that the effect of antitumor immunity extends to the advanced setting.
Study Details
In the CLEOPATRA trial, patients with locally recurrent, unresectable, or metastatic disease were randomized to receive first-line trastuzumab/docetaxel plus either pertuzumab or placebo. Overall, tumor samples from 678 of 808 participants (84%) were evaluable for stromal tumor-infiltrating lymphocytes, including 519 (77%) archival samples and 155 (23%) freshly obtained samples collected ≤ 45 days before randomization. The median tumor-infiltrating lymphocyte value was 10%; freshly obtained samples had lower tumor-infiltrating lymphocyte values compared with archival samples (10.00% vs 15.00%, P = .00036).
Association With Survival
Median follow-up was 50 months for progression-free survival and 51 months for overall survival. On multivariate analysis, there was no significant association between tumor-infiltrating lymphocyte values and progression-free survival (adjusted hazard ratio [HR] = 0.95, P = .063). For overall survival, each 10% increase in stromal tumor-infiltrating lymphocytes was significantly associated with longer overall survival (adjusted HR = 0.89, P = .0014).
The treatment effect of pertuzumab did not differ significantly by stromal tumor-infiltrating lymphocyte value for either progression-free survival (adjusted HRs = 0.94 for pertuzumab and 0.99 for placebo for each 10% increment; P = .23 for interaction) or overall survival (adjusted HRs = 0.89 for pertuzumab and 0.95 for placebo for each 10% increment; P = .21 for interaction).
The investigators concluded: “In patients with advanced HER2-positive breast cancer treated with docetaxel, trastuzumab, and pertuzumab or placebo, higher [tumor-infiltrating lymphocyte] values are significantly associated with improved overall survival, suggesting that the effect of antitumour immunity extends to the advanced setting. Future clinical studies in this cancer subtype should consider [tumor-infiltrating lymphocytes] as a stratification factor and investigate whether therapies that can augment immunity could potentially further improve survival.”
The study was funded by F. Hoffmann-La Roche-Genentech and the Breast Cancer Research Foundation.
Sherene Loi, MD, of Peter MacCallum Cancer Centre, University of Melbourne, is the corresponding author of The Lancet Oncology article.
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